Wednesday, January 14, 2009

Vitamin A

By 1906 it was known that factors other than carbohydrates, proteins and fats were necessary to keep cattle healthy. In 1917 one such substance was independently discovered by two American research groups, Elmer McCollum at the University of Wisconsin, and Lafayette Mendel and Thomas Osborne at Yale University. McCollum recognised that there were more than one of these substances and designated the fat soluble entity Vitamin A and the water soluble factor Vitamin B. In 1934 Wald isolated from animal retina a substance he called retinene. Morton in 1944 suggested that this compound was the aldehyde of vitamin A, and called it retinaldehyde (rather than retinal). The correct structure of vitamin A was deduced in 1931 by Karrer who proposed the name axerophthol (Axerophtol in German), based on its action in preventing the eye disease xerophthalmia. The first synthesis was in 1947 by two Dutch chemists, David Adriaan van Dorp and Jozef Ferdinand Arens.
Vitamin A found in foods that come from animals is called preformed vitamin A. It is absorbed in the form of retinol, one of the most usable forms of vitamin A. Sources include liver, whole milk, and some fortified food products. Retinol can be made into retinal and retinoic acid in the body. Provitamin A is found in colorful fruits and vegetables and is called carotenoid. It can be made into retinol in the body. Common provitamin A carotenoids found in foods that come from plants are beta-carotene, alpha-carotene, and beta-cryptoxanthin. Among these, beta-carotene is most efficiently made into retinol. Alpha-carotene and beta-cryptoxanthin are also converted to vitamin A, but only half as efficiently as beta-carotene.

Actually, of the 563 identified carotenoids, fewer than 10% can be made into vitamin A in the body. Some provitamin A carotenoids have been shown to function as antioxidants in laboratory studies; however, this role has not been consistently demonstrated in humans. Antioxidants protect cells from free radicals, which are potentially damaging by-products of oxygen metabolism that may contribute to the development of some chronic diseases.
Vitamin A is interesting for hematologists. The cell line HL60 is a myeloid leukemic cell line much loved by experimental hematologists. These blast-like cells can be made to differentiate into neutrophil granulocytes if exposed to vitamin A (vitamin D on the other hand turns them into monocytes) It appears that developing white cells have a receptor specifically designed for vitamin A.
Vitamin A deficiency is common in developing countries but rarely seen in the United States and Europe. Approximately 250,000 to 500,000 malnourished children in the developing world become blind each year from a deficiency of vitamin A. In Western countries, vitamin A deficiency is most often associated with strict dietary restrictions and excess alcohol intake. Strict dietary restrictions can also lead to zinc deficiency. Zinc is required to make retinol binding protein (RBP) which transports vitamin A. Therefore, a deficiency in zinc limits the body's ability to move vitamin A stores from the liver to body tissues.

Night blindness is one of the first signs of vitamin A deficiency. In ancient Egypt, it was known that night blindness could be cured by eating liver, which was later found to be a rich source of the vitamin. Vitamin A deficiency also contributes to blindness by making the surface of the eye very dry, thus it damages both the retina and the cornea.

As with other vitamins there has been interest in low storage levels of vitamin A that do not cause obvious deficiency symptoms. This supposedly mild degree of vitamin A deficiency is said to increase children's risk of developing respiratory and diarrheal infections, decrease growth rate, slow bone development, and decrease likelihood of survival from serious illness. Children living at or below the poverty level, who have children with inadequate health care or immunizations, especially those from immigrant communities and those with abnormalities of fat absorption are believed to be especially at risk.
Unless a person falls into one of these groups it is entirely likely that a normal diet will provide sufficient vitamin A. Three ounces of liver, for example, provides five times the daily requirement. Vegetarians and those who do not take dairy products will have to rely on the conversion of pro-retinoids from vegetables like carrots, cabbage, spinach or broccoli.
For those who like to take megadoses of vitamins, Vitamin A is one to be wary of. Overdoses are possible and can cause birth defects, liver abnormalities, reduced bone mineral density that may result in osteoporosis, and central nervous system disorders. The pro-retinoids have also been recommended as a prophylactic against cancer. A very large study of the use of beta-carotene had to be stopped when it was found that there was a 46% increase in lung cancer in those taking beta-carotene compared with controls.
However, retinoids can be used as medicines. For about 15 years synthetic retinoids (Roaccutane® or Accutane®)) have been used to treat certain skin diseases such as acne and psoriasis, and another retinoid, all trans retinoic acid (ATRA) is used to treat acute promyelocytic leukemia. Nevertheless, even these drugs should be avoided by those likely to get pregnant, and liver function tests should be monitored.
The daily requirement for vitamin A depends on your body size, but it is about 3000 international units and the safe upper limit of intake is 10,000 international units. 10,000 international unit is equivalent to about 3000 micrograms.


bob larkin said...

This is great stuff. Thanks for doing this. I look forward to the continuing series.

Brian Koffman said...

I am reminded of the Arctic explorers who died of Vitamin A toxicity after eating bear liver.